The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
hAda3 regulates p14ARF-induced p53 acetylation and senescence
Abstract
Acetylation is thought to be a key event for p53 activation. We demonstrate that p14ARF-induced senescence of human mammary epithelial cells (MEC) is associated with p53 acetylation and requires hAda3, a component of histone acetyltransferase complexes and a p53 transcriptional coactivator. Expression of the N-terminal domain of hAda3 that binds p53 but not p300 blocked p14ARF-induced p53 acetylation and protected MECs from senescence. Consistent with these findings, the human papillomavirus 16 E6 mutant Y54D, which selectively targets hAda3 but not p53 for degradation and protects MECs from p14ARF-induced senescence, inhibited p53 acetylation. In H1299 cells, hAda3 overexpression increased p300-mediated p53 acetylation, which conversely decreased following small interfering RNA (siRNA) knockdown of hAda3. Moreover, depletion of hAda3 by siRNA inhibited endogenous p53 acetylation and accumulation of p21cip1 in response to ectopic p14ARF. These studies reveal that, in addition to its known ability to inhibit Mdm2-mediated p53 degradation, p14ARF signals through hAda3 to stimulate p53 acetylation and the induction of cell senescence.
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“E6 has also been shown to abrogate the transactivation of p53-responsive genes via interactions with CBP/p300, [181,182,183], with hADA3 [184,185,186], and by destabilizing TIP60 [185]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [185]
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Cites
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MethodDNA damage activates p53 through a phosphorylation–acetylation cascade
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p53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage
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Role of the Ada2 and Ada3 transcriptional coactivators in histone acetylation.
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Role of p14ARF in Replicative and Induced Senescence of Human Fibroblasts
Wei, W., Hemmer, R. M., & Sedivy, J. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6748-6757.2001 · Cited by 217
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Cited by
Critical pathways in cellular senescence and immortalization revealed by gene expression profiling
Fridman, A. L., & Tainsky, M. A. (2008) · Oncogene · doi:10.1038/onc.2008.213 · Cited by 385
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Metadata
- Authors
- Sekaric, P., Shamanin, V. A., Luo, J., & Androphy, E. J.
- Venue
- Oncogene
- Published
- 2007-04-23
- Volume
- 26
- Issue
- 43
- Pages
- 6261-6268
- ISSN
- 0950-9232
- 1476-5594
- Cited by
- 28
- References
- 5
- Language
- en
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